Tube system for reconstructing of hollow organs

ABSTRACT

A tube system ( 1 ) for reconstructing a hollow organ, comprising a tube ( 2 ) for draining a substance, like e.g. urine, wherein the tube ( 2 ) for draining the substance is arranged within an outer tube ( 5 ) and that the space ( 4 ) between the two tubes ( 2, 5 ) is provided for the application of cells, and wherein the outer tube ( 5 ) is formed by a membrane ( 5 ) permeable for the cells to be applied, in particular a micro-perforated membrane ( 5 ).

The invention relates to a tube system for reconstructing a hollow organcomprising a tube for draining substances.

Such a tube system can be used in medicine so as to form a substitute ofdefective hollow organs or parts thereof occurring in case of congenitalanomalies, tumour resections or other impairments which can causedisfunctioning of the organ. Such tube systems are especially useful forthe formation or reconstruction of the urethra.

In reconstructing hollow organs like urethra tubes of the most varyingmaterials have been used so far in this special field of medicine, suchas synthetic materials as well as various types of tissue as freeimplants, vessel-containing skin parts, autologous buccal mucosa ormucosa of the bladder and epidermis cells for lining purposes. Thistechnique, however, involves considerable complications, such asimmunological rejection of the foreign matter or foreign tissue. In caseof urethra linings, it has not yet been achieved to protect theunderlying tissue from the aggressive action of urine. Fistulae,perforations and stenoses of the reconstructed urethras are theconsequences thereof.

A new development of reconstruction techniques in connection with theformation of urethras has been presented in a contribution by Bach etal. at the 30^(th) anniversary of the Deutsche Vereinigung fürPlastische Chirurgie (German Association for Plastic Surgery), Sep.15-16, 1999 at Seeon, Germany, wherein the construction of an artificialurethra by transplanting urothelial cells was illustrated. Inparticular, a catheter is implanted so as to cause an interconnectedtubular construct formed by tissue; the catheter is then removed, and asecond thinner catheter with autologous in vitro-cultured urothelialcells for lining the tissue space is inserted. A further, flexiblecathether is then used to form a connection between the generatedartificial urethra and the urinary bladder. In doing so it is a problemthat at given time intervals (e.g. of a few weeks each), catheters mustbe newly inserted, which, on the one hand, is stressful for the patientand requires increased medical expenditures since several surgicalinterventions are necessary, and which, on the other hand, results in aconsiderable time delay of the entire transplantation, orreconstruction, respectively. Moreover, several different apparatusesare required, resulting in complex handling and high expenditures.

Therefore, it would be of importance to provide a remedy in order toreduce insufficient functional results and the patients' high morbidity.

Therefore, it is an object of the invention to provide a tube system ofthe type initially defined enabling, in an advantageous manner, a safedrainage of substances and a formation of the hollow organ usingtransplanted autologous cells so as to re-establish the protectivefunction of the cells in the interior of the hollow organ.

The tube system according to the invention and of the type initiallydefined is characterised in that the tube for draining substances isarranged within an outer tube, and that the space between the two tubesis provided for the application of cells, and that the outer tube isformed by a membrane, in particular a micro-perforated membrane, whichis permeable in respect to the cells to be applied.

In the present tube system, the inner tube arranged within the outertube advantageously allows for a transportation of substances or fluidswithout thereby negatively affecting the hollow organ construct to beformed. At the same time, the space provided between the inner tube andthe membrane-formed outer tube allows the tissue to generate, for whichpurpose, in particular, an application of appropriate protective,preferably autologous cells cultured in vitro is performed, this beingdone through the said membrane, from the inside to the outside. Onaccount of this permeability, in particular of the micro-perforations,the required penetration of the cells to be applied is attained, and bymigration and proliferation of these cells in the immediate vicinity, anundisturbed lining of the inner tissue space of the hollow organ withthe appropriate protective cells is enabled. For this purpose it issuitable if the micro-perforations have a diameter in the order of 300μm; with such a size the cells can penetrate, as desired, therethroughwithout any problem and, on the other hand, any possible clogging of themicro-perforations can be avoided.

It should be mentioned that it is already known, for instance, from WO92/09311 A, or U.S. Pat. No. 5,575,815 A, that cells or other bioactivematerials may be delivered from an outer lumen into blood or the likepassing through an inner lumen of the respective catheter system.Accordingly, vascular protheses are concerned here, and it is the innertube which is penetrable to bioactive materials.

The tube system according to the invention preferably is provided withan epithelial lining.

The inner tube of the tube system according to the invention preferablyis made of silicone. Silicone is not only well suitable for medicalapplications, it also provides a stable tube system for an advantageoussupporting function in the manner of a “splinting” of the surgicalwound.

The micro-perforated membrane may be made of a natural or a syntheticpolymer, such as of polylactic acid (PLA), polyglycolic acid (PGA),polyglycol-polylactic acid (PGLA), fibrin or collagen. Such membranesare tissue-tolerable, durable and resistent. It is also particularlyadvantageous if the membrane material is bio-absorbable.

Preferably, the tube system has a sealing so as to prevent substances tobe drained from entering into the space between the tubes or into theregion of the tissue formation. Accordingly, it is advantageous if theinner tube has an associated sealing member, preferably a balloon.Advantageously, the balloon is inflatable so as to allow in connectionwith the inner tube for a continuous drainage of the liquid, like e.g.urine from a urinary bladder in the manner of a balloon catheter.

Furthermore, it is advantageous if the space between the tubes isconnected with at least one hose or tube for application of the cells,preferably in the form of a suspension. By aid of this hose, protectivecells may simply be delivered into the space between the tubes, fromwhere the cells may get through the membrane to the inner side of thehollow organ construct. For such a procedure, the hose suitableprotrudes beyond the aperture outwardly directed (the orifice) for asimplest insertation of cells as possible. The hose has a substantiallysmaller diameter than the inner tube.

To allow a particularly efficient cell application, a syringe fittingmeans for injecting cells, preferably in the form of a suspension, isprovided-at one end of the hose. This allows for practical handling.

Advantageously, the cells to be inserted are autologous cells, inparticular urothelial cells which are cultured in vitro and are thensuspended in a transportation matrix, preferably a fibrin adhesive. Indoing so it is achieved that the cells are introduced through thetransplant into the adjacent connective tissue space by means of thetube system of the invention without causing any rejections or otherimmunological disorders. In detail, it is, for instance, possible togrow and proliferate in vitro the patient's own tissue cells obtained bybiopsy. The suspension in a fibrin adhesive as transportation matrixallows for gentle transportation and a reliable transfer of the in-vitrogrown urothelial or, general tissue cells, respectively.

The present tube system is to be dimensioned in dependence on the shapeof the hollow organ to be reconstructed, and it may, for instance, beformed as a double-lumen catheter system, with the inner lumen formingthe inner tube and the outer lumen forming the outer tube.

The tube system may also contain already applied cells in theintermediate space, such as for example urothelial cells. Suchembodiment is particularly advantageous if the cells are maintained in adeep-frozen state and are thawed when needed, prior to a surgicalintervention, and are inserted into the urethra. Since cells arestorable under deep-frozen conditions for a certain period of time, suchcells can be made available at short notice together with the tubesystem. The removal of the endogenous cells from the patient's defectivehollow organ and the subsequent in vitro cell proliferation may takeplace beforehand, at a preliminary examination being necessary anyway,so as to guarantee the immunological advantages when re-inserting theautologous cells.

Summing up, as advantages of the present invention it may be emphasizedthat a tube system or a double-lumen catheter is provided which, on theone hand, primarily can be introduced orthotopically in the course of asurgical intervention or during the reconstruction of the connectivetissue portion of a hollow organ (e.g. urethra) and by which, on theother hand, a continuous drainage of substances, e.g. urine is attainedunder sealing, preferably by means of an inflatable balloon, with asimultaneous splinting and protection of the surgical wound beingensured. Moreover, the present tube system allows for the primary andsecondary settlement of the connective tissue space surrounding the tubesystem with cultured autologous cells transported in a transportationmatrix by way of the outer tube.

An examplary embodiment of the present invention will now be describedin more detail with reference to the drawing. Here, the single drawingFIGURE gives a schematic illustration of a tube system in the form of adouble-lumen catheter which is inserted for reconstructing an urethra.

In particular, the drawing shows the tube system being a double-lumencatheter 1 comprising within an inner tube 2 a closed inner lumen havinga bladder-side aperture and an outer aperture for draining substancesfrom the urinary bladder 3, as well as an outer lumen 4. This outerlumen 4 is outwardly delimited by a membrane 5 being the outer tubewhich is provided with micro-perforations 6. When reconstructing anurethra the area of which is schematically indicated at 7 in thedrawing, this membrane 5, or outer tube, respectively, comes to lie inthis urethra region 7, and cells supplied to the space between the tubes2 and 5, i.e. to the outer lumen 4, are able to pass through themicro-perforations 6 so as to consequently initiate the formation of aninner tissue space of the urethra. On the open end of the catheter 1which is directed towards the bladder, a sealing is provided in the formof a conventionally inflatable balloon 8 which prevents an unintendedentry of urine into the region of the tissue formation, whereby acontinuous emptying of the bladder 3 is enabled. This balloon 8,furthermore, prevents the system sliding out of the urethra and ensurescontact to the bladder. The flow direction of the urine has beenindicated by an arrow A in the drawing.

A hose or tube 9 is introduced into the space 4 between the inner tube 2and the outer tube 5 so as to supply the space 4 with theafore-mentioned cells from the outside 10. At the outer, open end of thehose 9 located opposite of the balloon 8, i.e. at the side of theorifice, a—merely quite schematically indicated—syringe fitting means 11is provided which ensures that the direct cell application can simply beeffected by means of an injection syringe.

Via this syringe fitting means 11, thus, in-vitro cultured autologousurothelial cells are injected as a suspension in a fibrin adhesive byusing the syringe (not illustrated). This facilitates an efficient,gentle cell application and consequently ensures a careful migration andsettlement of the autologous urothelial cells in the interior of theurethra.

The inner tube 2 forming the inner lumen preferably consists ofsilicone, whereas the micro-perforated membrane 5 delimiting the outerlumen 4, in particular, is made of a natural or synthetic, bioabsorbablepolymer, such as poly-lactic acid (PLA), polyglycol-poly-lactic acid(PGLA), fibrin or collagen. Likewise, the hose 9 may be made, e.g., ofsilicone.

The inner tube 2, together with the inflatable balloon 8, is designed asa conventional balloon catheter, and therefore, no further explanationis required.

Thus, a tube system 1 is obtained which is, on the one hand, relativelysimple to handle, and which, on the other hand, constitutes an effectivepossibility for reconstructing, e.g. an urethra with autologousurothelial cells.

1. An urethra tube system comprising: an inner tube having a lumenconfigured to drain urine; an outer tube having a lumen configured anddimensioned to receive the inner tube, wherein a space is definedbetween the outer tube and the inner tube when the inner tube isreceived within the outer tube; and isolated cells positioned within thespace defined between the inner tube and the outer tube, wherein thecells are capable of reconstructing the urethra; wherein the outer tubeincludes a micro-perforated membrane comprising a bioabsorbablepermeable material to which the cells are applied.
 2. The urethra tubesystem according to claim 1, wherein the membrane formsmicro-perforations having a diameter of around 300 μm.
 3. The urethratube system according to claim 1, wherein the inner tube is comprised ofsilicone.
 4. The urethra tube system according to claim 1, wherein themembrane is comprised of a natural polymer.
 5. The urethra tube systemaccording to claim 1, wherein the membrane is comprised of a syntheticpolymer.
 6. The urethra tube system according to claim 1, wherein theinner tube includes a sealing member comprising a balloon.
 7. Theurethra tube system according to claim 1, including a hose meansextending into the space for application of the cells.
 8. A The urethratube system according to claim 7, wherein the hose means is configuredfor the application of cells in the form of suspension.
 9. The urethratube system according to claim 7, wherein an end of the hose is attachedto a syringe fitting means.
 10. The urethra tube system according toclaim 1, wherein the inner tube and outer tube comprise a double-lumencatheter for drainage of urine and the simultaneous lining of theurethra with cells.
 11. The urethra tube system according to claim 1,wherein the cells for lining the inner space of the urethra are disposedwithin the space.
 12. The urethra tube system according to claim 1,wherein the cells include urothelial cells.
 13. The urethra tube systemaccording to claim 12, wherein the urothelial cells include in-vitrocultured autologous urothelial cells suspended in a transportationmatrix.
 14. The urethra tube system according to claim 13, wherein thetransportation matrix includes a fibrin adhesive.
 15. The urethra tubesystem according to claim 1, wherein the outer tube has a diameter of0.8 mm to 1.5 mm, preferably 1.2 mm.
 16. The urethra tube systemaccording to claim 15, wherein the outer tube has a diameter of 1.2 mm.17. The urethra tube system according to claim 1, wherein the inner tubehas a diameter of 0.5 mm to 1.2 mm.
 18. The urethra tube systemaccording to claim 17, wherein the inner tube has a diameter of 0.8 mm.